Progesterone and vascular function: mechanisms and therapeutic implications in cardiovascular disease

Progesterone, the first sex hormone ever discovered, has a long history. Yet, it gained prominence in research during the 1930s. Currently, our understanding of progesterone goes beyond its role in the reproductive system, also encompassing the cardiovascular system. Studies have reported on the protective role played by this hormone in the cardiovascular system, which is primarily due to its actions on the vasculature. Progesterone stimulates vasoactive factors, modulates lipid profiles, reduces inflammatory responses, inhibits platelet aggregation and cell proliferation, and lowers blood pressure, thereby contributing to the reduction of cardiovascular disease risk. However, for a long time, hormone replacement therapy relied on the use of progestins, synthetic compounds that failed to replicate the beneficial effects of progesterone and often cause various adverse effects, which cannot be attributed to progesterone itself. In this context, this review compiles the most recent findings regarding the actions of progesterone in the vascular system, while also presenting a historical overview that contextualizes the research in both clinical and experimental areas related to progesterone. Thus, we seek to clarify the unique role played by progesterone in the cardiovascular system, dispelling misconceptions about its effects and discussing its therapeutic prospects.